Yuxiang Sun, M.D., Ph.D.
Assistant Professor
USDA/ARS Children’s Nutrition Research Center,
Huffington Center on Aging,
Departments of Pediatrics and Molecular and Cellular Biology Education,
Baylor College of Medicine
E-mail: yuxiangs@bcm.edu
Phone: 713-798-7167
Education:
Ph.D.: University of Manitoba, Winnipeg, Manitoba, Canada
Postdoctoral training: Huffington Center on Aging, Baylor College of Medicine, Houston
Research Interests
The Role of Ghrelin and Ghrelin Receptor in Obesity and Diabetes
The incidence of diabetes has reached epidemic proportions. More alarmingly, diabetes has become a major disease of aging: One in five Americans over age 60 now has Type 2 diabetes. The primary cause of diabetes in the elderly is increased insulin resistance precipitated by increased fat mass and decreased muscle mass. Insulin resistance eventually leads to pancreatic beta cell failure, which results in diabetes.
Ghrelin is the only circulating orexigenic hormone known to increase growth hormone (GH) release, stimulates appetite and promotes obesity. Using our ghrelin and ghrelin receptor (aka, growth hormone secretagogue receptor, GHS-R) knockout mice, we demonstrated that ghrelin’s effects on GH release and appetite are mediated through GHS-R (Ref 9 & 10). We also made the novel observation that ghrelin deficiency improves pancreatic beta cell function and peripheral insulin sensitivity (Ref 5).
Our short-term goals are: 1) to study the roles of ghrelin and its receptor in pancreatic islet biology (regulation on counter-regulatory hormones such as insulin and glucagon); 2) to study the roles of ghrelin and its receptor in central (brain) glucose sensing and peripheral (liver, muscle and fat) insulin sensitivity; 3) to elucidate the cellular and molecular mechanisms of ghrelin and its receptor in obesity and diabetes. Physiological and pharmacological approaches are carried out in knockout mice, primary and tissue culture model systems to study this signal pathway.
Longevity and healthspan are closely related to insulin sensitivity. Our long-term goals are: 1) to obtain a better understanding of the pathophysiology and interplay of obesity, diabetes and aging; 2) to shed light on the cellular and molecular mechanisms of these pathophysiological states. Ultimately, we hope to improve human quality of life by developing new therapeutic approaches for preventing and/or treating obesity and diabetes, as well as delaying and/or preventing the onset of age-related diseases.
Representative Publications:
1.Sun Y, Butte NF, Garcia JM and Smith RG. (2008). Characterization of adult ghrelin and ghrelin receptor knockout mice under positive and negative energy balance. Endocrinology 149:843-850.
2.Sun Y*, Asnicar M and Smith RG. (2007). Central and peripheral roles of ghrelin on glucose homeostasis. Neuro-endocrinology 86:215-228. *corresponding author
3.Dixit VD, Yang H, Sun Y, Weeraratna AT, Youm YH, Smith RG and Taub DD. (2007). Ghrelin promotes thymopoiesis during aging. Journal of Clinical Investigation 117:2778-2790.
4.Sun Y*, Garcia JM and Smith RG. (2007). Ghrelin and growth hormone secretagogue receptor expression in mice during aging. Endocrinology 148:1323-1329. *corresponding author
5.Sun Y, Asnicar M, Saha PK, Chan L and Smith RG. (2006). Ablation of Ghrelin Gene Improves the Diabetic but not Obese Phenotype of ob/ob Mice. Cell Metabolism 3:379-386.
6.Wang G-L, Shi X, Salisbury E, Sun Y, Albrecht JH, Smith RG and Timchenko NA. (2006). Cyclin D3 maintains growth-inhibitory activity of C/EBPalpha by stabilizing C/EBPalpha-cdk2 and C/EBPalpha-Brm complexes. Molecular and Cellular Biology 26:2570-2582.
7.Toshinai K, Yamaguchi H, Sun Y, Smith RG, Yamanaka A, Sakurai T, Date Y, Mondal MS, Shimbara T, Kawagoe T, Murakami N, Miyazato M, Kangawa K and Nakazato M. (2006). Des-acyl Ghrelin Induces Food Intake by a Mechanism Independent of the Growth Hormone Secretagogue Receptor. Endocrinology 147:2306-2314.
8.Smith RG, Betancourt L and Sun Y. (2005). Molecular endocrinology and physiology of the aging central nervous systems. Endocrine Reviews 26:203-250.
9.Sun Y, Wang P, Zheng H and Smith RG. (2004). Growth Hormone Secretagogue Receptor (GHS-R) mediates ghrelin’s effects on GH release and appetite. Proc Natl Acad Sci USA 101:4679-4684.
10. Sun Y, Ahmed S and Smith RG (2003). Deletion of ghrelin impairs neither growth nor appetite. Molecular and Cellular Biology 23:7973-7981.